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Antidepressants Work, and Depression Severity Does Not Matter

Summary and Comment |
March 12, 2012

Antidepressants Work, and Depression Severity Does Not Matter

  1. Peter Roy-Byrne, MD

Effects are greatest in children, but are significant for all, in a study examining patient-level data from 41 studies focusing on two antidepressants.

  1. Peter Roy-Byrne, MD

Suggestions that antidepressants work only in severely depressed patients have been based largely on analyses comparing different study outcomes — i.e., fewer overall study effects were found in studies that had, on average, less-depressed patients — and on the existence of many unpublished studies that did not show antidepressant efficacy, suggesting that published studies overestimated efficacy. Only one small analysis (JW Psychiatry Feb 1 2010) of six already published and highly selected studies used individual patient-level data (N=718) to examine the issue of less effect in less-depressed patients.

These researchers obtained longitudinal, patient-specific data from all sponsored, published and unpublished, placebo-controlled studies on fluoxetine (20 trials; 705 youths, 2635 adults, and 960 geriatric patients) and venlafaxine (21 trials; 4882 adults). All patients had at least minimal depression severity at baseline. Rates of change through 6 weeks were significantly greater with antidepressant than with placebo overall and in each age group. Overall response and remission rates yielded number needed to treat (NNT) of 5 and 7, respectively. Response and remission rates were significantly greater for fluoxetine than placebo for youth (NNT, 4 and 3) and adults (NNT, 5 and 6) but not geriatric patients (NNT, 17 and 39). Most important, no relationship was found between how depressed a patient was and that patient's response to antidepressants.

Comment

This analysis of more than 9000 patients shows that antidepressants work regardless of the severity of the depression. Moreover, antidepressant response often takes more than the 6 weeks analyzed here, suggesting that these effects may be underestimated. That older populations showed the lowest rate of change is interesting, but this finding must be considered preliminary because only four geriatric studies contributed data. Finally, these results add to concerns that meta-analyses summarizing effects across studies with different designs and outcomes, while sometimes useful, can lead to erroneous conclusions.

Citation(s):

Reader Comments (7)

Walter Doege

This response of Prof. Roy-Byrne is a remark of major importance and disregarding other aspects I want to emphasize as clinician the methodological and cognitive dimensions of reading articles especially reaserch studies and original articles. Reading articles is someway different from reading a textbook or review article cause at the final reading conclusion must be a cognitive mistake and misundestanding. Especially original articles and reseach article on basic science brings to me some kind of difficulty not only regarding my clinician condition but the methodological and other cognitive abilities and skills that in a hard work daily basis practice yhe translation of basic research to clinical setting I feel difficult. This response is of major importance. I guess Psychiatric Medicine is a science based practice and an art.

Competing interests: None declared

Peter Roy-Byrne, MD

This study differs from meta-analyses, which combine average summary scores from studies. Instead, this analysis took data on individuals and pooled them together (a pooled analysis). Thus, the caveat about meta- analysis does not apply to the current study. Once you pool the data, the STUDY variability is no longer operative. Instead we are able to see INDIVIDUAL variability, which is what is required to truly address the question.

Competing interests: Summary author

Walter Doege

The different sources and different research methods (clinical observation, published trials, published reports, unpublished clicical obervations) is one aspect of psychiatry, an integrative specialty that doesn't have the patognomonic and/or objective data from diagnostic methods especially biomarkers that all other medical specialties have. How a psychiatrist thinks is somewhat unique: knowledge, experience and clinical expertise recquires a specific cogntive skill: psychiatry is medicine and differently from rheumatology I consider that clinical aspects are still the main aspects: natural course of disorders, drug effectiveness, remission, recurrence, refractory disorders and other medical parameters works differently in a cognitive reflection. This article points out what I do observe: depressive disorders must be treated with drug treatment antidepressants regardless clinical severity and for more than 6 weeks. Six months after an adaptational period regarding dosage and tolerance is a time sufficient for observation of drug effectiveness still when considering polidrug pharmachotherapy. And I consider two years a mininal period for observe remisision. Till nowadays these parameters are different from other medical specialties. The overlap and comorbidity between rheumatologic and psychiatric conditions is another interesting point. Any physician must hear what patient says: his history, his family and the social network are all important aspects for good and correct medical practice.

Competing interests: None declared

James Recht

According to the JWatch reviewer, "...these results add to concerns that meta-analyses summarizing effects across studies with different designs and outcomes, while sometimes useful, can lead to erroneous conclusions." That statement applies to the paper under consideration, doesn't it?

Competing interests: None declared

John GILBERT

It has been clear for years in primary care that the published studies did not reflect the same population that we were dealing with. The referral rate to specialist care is very low for this kind of patient, essentially only those few who were not responding to medication at normal doses.

Competing interests: None declared

Marcelo D. Schafranski

Is it possible to estimate the difference between remission rates observed in the published trials and compare them to the same outcome obtained from the publlished reports? And how large is the remission NNT for the unpublished data regarding remission? In my opinion, these are crucial information that must be reported.

Competing interests: None declared

Walter Doege

This article points out what I observe in my clinical practice: choose an antidepressant drug after a careful diagnostic procedure and institute a drug treatment regardless severity of depression and comorbidities is safe and effective. I observe that response is time dependent and longer than 6 weeks. Drug dosage is usually lower for mantainace drug treatment longer than 6 months and in many cases far than two years. And the drugs are common and safe.

Competing interests: None declared

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